U.S. patent number 4,883,958 [Application Number 07/285,516] was granted by the patent office on 1989-11-28 for interface for coupling liquid chromatography to solid or gas phase detectors.
This patent grant is currently assigned to Vestec Corporation. Invention is credited to Marvin L. Vestal.
United States Patent |
4,883,958 |
Vestal |
November 28, 1989 |
**Please see images for:
( Certificate of Correction ) ** |
Interface for coupling liquid chromatography to solid or gas phase
detectors
Abstract
Improved techniques are provided for interfacing liquid
chromatography with gas phase and solid phase detectors. Heated
liquid effluent including sample solute of interest and solvent is
sprayed into a desolvation chamber, where controlled vaporization
of the solvent occurs while maintaining sample particles of
interest. A carrier gas is added to the desolvation chamber, and
the discharged aerosol is transmitted through a uniform
cross-sectional flow path to a condenser, gas diffusion cell, or
other solvent removal device. Substantially all transmitted solvent
is thereby removed, with the carrier gas and substantially all of
the sample particles of interest passing to the detector for
analysis. The interface of the present invention is applicable to
thermospray technology and other spraying techniques resulting in
vaporization and nebulization of the LC effluent. The methods and
apparatus of the present invention may be reliably employed with
various gas phase or solid phase detectors for sample analysis, and
may be used over a wide range of chromatographic conditions.
Inventors: |
Vestal; Marvin L. (Houston,
TX) |
Assignee: |
Vestec Corporation (Houston,
TX)
|
Family
ID: |
23094585 |
Appl.
No.: |
07/285,516 |
Filed: |
December 16, 1988 |
Current U.S.
Class: |
250/288; 250/281;
250/282 |
Current CPC
Class: |
G01N
30/7273 (20130101); H01J 49/0445 (20130101); H01J
49/049 (20130101); G01N 30/30 (20130101); G01N
30/7213 (20130101); G01N 30/7253 (20130101); G01N
30/7286 (20130101); G01N 30/7293 (20130101); G01N
2030/8423 (20130101) |
Current International
Class: |
G01N
30/72 (20060101); G01N 30/00 (20060101); H01J
49/04 (20060101); H01J 49/02 (20060101); G01N
30/84 (20060101); G01N 30/30 (20060101); H01J
041/04 () |
Field of
Search: |
;250/281,282,288,288A |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
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|
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|
|
0102553 |
|
May 1986 |
|
JP |
|
61-107156 |
|
May 1986 |
|
JP |
|
Other References
"Monodisperse Aerosol Generation Interface for Combining Liquid
Chromatography with Mass Spectroscopy", Willoughby et al., School
of Chemistry, Georgia. .
"Improvements in a Particle Beam LC/MS Interface", Apffel, et al.,
6/88, 36th ASMS Conference on Mass Spectrometry and Allied Topics.
.
"Positive-and Negative-Ion Chemical Ionization Mass Spectrometry of
Aldicarb and its Derivatives by Particle Beam HPLC/MS", Lynn, et
al., 6/88, 36th ASMS Conf. .
"Analysis of Drugs of Abuse by Particle Beam LC/MS", Apffel et al.,
6/88, 36th ASMS Conference on Mass Spectrometry and Allied Topics.
.
"LSMIS of Intact Oligosaccharides: Comparison of Sensitivity and
Spectral Quality Among Selected Derivatives", Poulter et al., 6/88,
36th ASMS Conference. .
"Studies of Anabolic Steroids by Thermabeam LC/MS", Dilts et al.,
6/88, 36th ASMS Conference on Mass Spectrometry and Allied Topics.
.
"Electron Impact Ionization Mass Spectra of Polystyrene Oligomers
by Thermabeam LC/MS", Jones, 6/88, 36th ASMS Conference on Mass
Spectrometry and Allied. .
"Secondary Ion Mass Spectrometry of Solute Particle Beams by
Thermabeam LC/MS", Willoughby et al., 36th ASMS Conference on Mass
Spectrometry and Allied Topics. .
"Polymeric Fluorenyl Reagent for the Derivatization of Polyamines
in Biological Fluids", Chou et al., Abstract No. 247. .
"Supercritical Fluid Chromatographic/Mass Spectrometric Studies of
Environmental Samples", Games et al., Abstract No. 248. .
"MAGIC: Basic Studies in Transport and Transport Efficiency", Kirk
et al., Abstract No. 249. .
"Chromatographic Performance and Applications of the MAGIC LC/MS
Interface", Harris et al., Abstract No. 250. .
"Ion Spray LC/MS Determination of Neuro Peptides with Atmospheric
Pressure Ionization", Lee et al., Abstract No. 251. .
"Comparison of Different Absorbance Detection Techniques LC-UV-MS",
Dourdeville et al., Abstract No. 252. .
"An Improved Thermospray LC/C1/E1 Ion Source for Structural
Elucidation in Combined Liquid Chromatography/Mass Spectrometry",
Vestal et al., Abst. No. 253. .
"Electron Impact Mass Spectra with Thermabeam LC/MS", Willoughby et
al., Abstract No. 255. .
"Design of a New Liquid Chromatographic System for LC-UV-MS",
Cassis et al., Abstract No. 256. .
"Integrated Thermospray and Thermabeam Sample Introduction for
LC/MS and SFC/MS", Buchner, Abstract No. 257. .
"Revenants in Chemical Analysis", Lodder et al., Abstract No. 258.
.
"Particle Concentration Fluorescence Immunoassay for Tissue
Plasminogen Activator", Sportsman et al., Abstract No. 329. .
"Structural Elucidation in Biomedical and Pharmaceutical Analysis
via Mass Spectroscopy Using Thermabeam and Thermaspray LC/MS",
Sheehan, Abstract #330. .
"Legally Defensible Data on Drugs of Abuse by Thermabeam LC/MS",
Pizzitola et al., Abstract No. 668. .
"Evaluation of Thermospray Liquid Chromatography-Mass Spectrometry
for Drugs of Abuse", Vestal, Abstract No. 669. .
"Determination of Spent Solvent Wastes in Water By Thermospray
Liquid Chromatography-Mass Spectrometry", Vestal, Abstract No.
1260. .
"New Ways to Get Excited with LC/MS and Environmentally Significant
Compounds", Pizzitola et al., Abstract No. 1261. .
"Solid Phase Extraction for Determination of Urea and Carbamate
Pesticides in Ground Water", Englel et al., Abstract No. 1337.
.
"Particle Beam Liquid Chromatography Mass Spectrometry (PB/LC/MS):
A New Technique Applied to Determinations of Environmental,
Forensic and Defense Interest", Sauter et al., Abstract No. 759.
.
"Fundamental Studies of High Efficiency Sputtering System for
Atomic Spectroscopy", Piepmeier et al., Abstract No. 760. .
"Capillary Diameter Effects on Thermospray Sample Introduction to
ICP-AES", Koropchak et al., 1/88, Winter Conference on Plasma
Spectrochemical Analysis. .
"Thermospray Interfacing for Flow Injection Analysis with
Inductively Coupled Plasma Atomic Emission Spectrometry", Koropchak
et al., 4/86. .
"A Comparison Between Thermospray and Particle Beam LC/MS for
Environmental Applications", Apffel et al., 7/88, Symposium on
Waste Testing & Quality Assurance..
|
Primary Examiner: Fields; Carolyn E.
Assistant Examiner: Miller; John A.
Attorney, Agent or Firm: Browning, Bushman, Zamecki &
Anderson
Claims
What is claimed is:
1. An improved interface for receiving liquid effluent including
sample solute of interest and solvent from a liquid chromatographic
device and outputting sample particles of interest to a detector
for analysis of a sample, the interface comprising:
a desolvation chamber;
desolvation chamber heating means for heating the sprayed effluent
within the desolvation chamber to vaporize substantially all
solvent within the desolvation chamber while maintaining the sample
particles of interest in the desolvation chamber;
spraying means for discharging the heated liquid effluent into the
desolvation chamber;
gas supply means for inputting a carrier gas to the desolvation
chamber;
flow path means for transferring an aerosol including the carrier
gas, vaporized solvent, and the sample particles of interest from
the desolvation chamber; and
solvent removal means for receiving the aerosol and removing
substantially all of the vaporized solvent while outputting the
carrier gas and substantially all of the sample particles of
interest to the detector for analysis, the solvent removal means
including a cell housing, a gas diffusion membrane within the cell
housing and separating the cell housing into a primary flow chamber
for receiving the aerosol and an adjoining secondary flow chamber
and supplemental carrier gas supply means for passing carrier gas
through the secondary flow chamber while aerosol is passed through
the primary flow chamber such that solvent vapor is diffused
through the membrane from the primary flow chamber to the secondary
flow chamber and is removed by the supplemental carrier gas.
2. A improved interface as defined in claim 1, further
comprising:
thermospray controller means for regulating thermal output of the
heating means to vaporize a substantial portion of the solvent from
the liquid chromatographic device prior to being discharged into
the desolvation chamber.
3. An improved interface as defined in claim 1, wherein the solvent
removal means further comprises:
condensor means for cooling the aerosol and condensing
substantially all the vaporized solvent therein into liquid
solvent.
4. An improved interface as defined in claim 3, further
comprising:
a liquid waste drain in fluid communication with the flow path
means for continuously outputting the condensed liquid solvent from
the condenser means while the aerosol is transferred through the
flow path means to the condenser means; and
the flow path means being configured such that substantially all
condensed liquid vapor within the condenser means flows through a
portion of the flow path means to the liquid waste drain in a
counterflow direction to aerosol flow through the portion of the
flow path means.
5. An improved interface as defined in claim 3, wherein the
condenser means further comprises:
first and second cooling means serially spaced for cooling the
aerosol at respective first and second serially spaced locations
within the condenser means; and
a transition section between the first and second cooling means for
revaporizing condensed solvent carried on the particles of interest
passing by the first cooling means and recondensing the solvent off
the particles of interest with the second cooling means.
6. An improved interface as defined in claim 3, further
comprising:
condenser temperature control means for controlling the temperature
of the aerosol passing through the condenser means for removing in
excess of 99% of the solvent vapor within the aerosol passing
through the flow path means such that a low concentration of
solvent vapor is output to the detector.
7. An improved interface as defined in claim 1, wherein
cross-sectional flow area of the flow path means remains
substantially uniform such that rapid expansion or contraction of
the aerosol is minimized or prevented.
8. An improved interface as defined in claim 7, wherein the
desolvation chamber, the flow path means, and the solvent removal
means are each configured such that abrupt directional changes of
flowing aerosol are avoided.
9. An improved interface as defined in claim 4, further
comprising:
a substantially uniform diameter flow tube defining the
cross-sectional flow area within the desolvation chamber, the flow
path means, and the solvent removal means.
10. An improved interface as defined in claim 1, wherein the flow
path means has a length at least thirty times the cross-sectional
diameter of the flow path means.
11. An improved interface as defined in claim 1, further
comprising:
carrier gas control means for regulating carrier gas flow rate into
the desolvation chamber such that the carrier gas flow rate is
greater than the flow rate of vapor discharged into the desolvation
chamber from the spraying means.
12. An improved interface as defined in claim 1, wherein:
a discharge end of the spraying means is positioned within the
desolvation chamber; and
the gas supply means inputs carrier gas within the desolvation
chamber circumferentially about the discharge end of the spraying
means such that the carrier gas flows within the desolvation
chamber axially toward the discharge end of the spraying means to
prevent the aerosol from contacting sidewalls of the flow path
means.
13. An improved interface as defined in claim 1, further
comprising:
vapor temperature sensing means for sensing the temperature of the
solvent vapor within the desolvation chamber and generating a
signal to the desolvation chamber heating means in response
thereto.
14. An improved interface as defined in claim 1, further
comprising:
temperature control means for regulating the desolvation chamber
heating means; and
the desolvation chamber heating means increases the temperature of
the particles of interest within the desolvation chamber to a
temperature approaching thermal equilibrium with the vaporized
solvent within the desolvation chamber.
15. An improved interface as defined in claim 3, further
comprising:
vapor temperature sensing means for sensing the temperature of the
solvent vapor in the condensing means and generating a signal to
the condensing means in response thereto.
16. An improved interface as defined in claim 3, wherein the
condensing means comprises:
cooling means for continually condensing at least a substantial
portion of the solvent vapor received by the condensing means;
a liquid drain for removing the condensed solvent from the cooling
means; and
a cyrogenic trap downstream from the cooling means for collecting
in solid form remaining solvent vapor which passes by the cooling
means, such that substantially only carrier gas and particles of
interest are passed to the detector.
17. An improved interface as defined in claim 16, further
comprising:
condenser temperature control means for regulating the cooling
means to maintain condensed solvent within the condenser means at a
temperature above the freezing point of the condensed solvent.
18. An improved interface as defined in claim 1, further
comprising:
the detector is a gas phase detector; and
vaporizing means for vaporizing the particles of interest output
from the solvent removal means to produce vapor for analysis by the
gas phase detector.
19. An improved interface as defined in claim 1, further
comprising:
a moving surface means; and
the particles of interest from the solvent removal means are
deposited on the moving surface means for analysis by the
detector.
20. An improved interface as defined in claim 1, further
comprising:
first and second momentum separators for removing carrier gas from
the particles of interest; and means for connecting the interface
to the detector, wherein the detector is an electron impact mass
spectrometer.
21. An improved interface as defined in claim 20, wherein:
each of the first and second momentum separators includes a nozzle
and an axially spaced skimmer for controlling the amount of carrier
gas passed with the particles of interest to the detector.
22. An improved interface as defined in claim 1, further
comprising:
reagent gas supply means for adding reagent gas to the carrier gas
input to the desolvation chamber; and means for connecting the
interface to the detector, wherein the detector is a chemical
ionization mass spectrometer.
23. An improved interface for receiving liquid effluent including
sample solute and solvent from a liquid chromatograhic device and
outputting sample particles of interest to a detector for analysis
of a sample, the interface comprising;
a desolvation chamber;
spraying means for discharging the liquid effluent into the
desolvation chamber;
heating means for heating the sprayed effluent within the
desolvation chamber to vaporize substantially all solvent within
the desolvation chamber while maintaining the sample particles of
interest in the desolvation chamber;
gas supply means for inputting a carrier gas to the desolvation
chamber;
solvent removal means for receiving the transmitted aerosol and
removing most of the vaporized solvent while outputting the carrier
gas and substantially all of the sample particles of interest to
the detector for analysis the solvent removal means including a gas
diffusion cell means for diffusing solvent from the aerosol while
outputting carrier gas and sample particles of interest to the
detector, the gas diffusion cell means having a cell housing, a gas
diffusion membrane within the cell housing and separating the cell
housing in a primary flow chamber for receiving the aerosol and an
adjoining secondary flow chamber and supplemental carrier gas
supply means for passing carrier gas through the secondary flow
chamber while aerosol is passed through the primary flow chamber
such that solvent vapor is diffused through the membrane from the
primary flow chamber to the secondary flow chamber and is removed
by the supplemental carrier gas; and
a waste drain for continuously outputting solvent from the solvent
removal means while the aerosol is transferred through the flow
path means.
24. An improved interface as defined in claim 23, further
comprising:
liquid effluent heating means for heating the liquid effluent prior
to entering the desolvation chamber; and
thermospray controller means for regulating thermal output of the
liquid effluent heating means to vaporize a substantial portion of
the solvent from the liquid chromatographic device prior to being
discharged into the desolvation chamber.
25. An improved interface as defined in claim 23, wherein the
solvent removal means comprises:
condensor means for cooling the aerosol and condensing
substantially all the vaporized solvent therein into liquid
solvent.
26. An improved surface as defined in claim 25, wherein the
condenser means further comprises:
first and second cooling means serially spaced for cooling the
aerosol at respective first and second serially spaced locations
within the condenser means; and
a transition section between the first and second cooling means for
revaporizing condensed solvent carried on the particles of interest
passing by the first cooling means and recondensing the solvent off
the particles of interest with the second cooling means.
27. An improved interface as defined in claim 23, further
comprising:
carrier gas control means for regulating carrier gas flow rate into
the desolvation chamber such that the carrier gas flow rate is
greater than the flow rate of vapor discharged into the desolvation
chamber from the spraying means.
28. An improved interface as defined in claim 23, wherein:
a discharge end of the spraying means is positioned within the
desolvation chamber; and
the gas supply means inputs the carrier gas within the desolvation
chamber circumferentially about the discharge end of the spraying
means such that the carrier gas flows within the desolvation
chamber axially toward the discharge end of the spraying means to
prevent the aerosol from contacting sidewalls of the flow path
means.
29. An improved interface as defined in claim 25, further
comprising:
first vapor temperature sensing means for sensing the temperature
of the solvent vapor within the desolvation chamber and generating
a signal to the heating means in response thereto; and
second vapor temperature sensing means for sensing the temperature
of the solvent vapor in the condensing means and generating a
signal to the condensing means in response thereto.
30. An improved interface as defined in claim 25, wherein the
condensing means comprises:
cooling means for continually condensing at least a substantial
portion of the solvent vapor received by the condensing means and
passing the condensed solvent to the waste drain; and
a cyrogenic trap downstream from the cooling means for collecting
in solid form remaining solvent vapor which passes by the cooling
means, such that substantially only carrier gas and particles of
interest are passed to the detector.
31. An improved interface as defined in claim 23, further
comprising:
vaporizing means for vaporizing the particles of interest output
from the solvent removal means to produce vapor for analysis by the
detector.
32. An improved interface as defined in claim 23, further
comprising:
flow path means having a substantially uniform cross-sectional area
for transferring an aerosol including the carrier gas, the
vaporized solvent, and the sample particles of interest from the
desolvation chamber such that rapid expansion or contraction of the
aerosol is minimized, the flow path means having a substantially
uniform cross-sectional area for transferring an aerosol including
the carrier gas, the vaporized solvent, and the sample particles of
interest from the desolvation chamber such that rapid expansion or
contraction of the aerosol is minimized.
33. An improved interface as defined in claim 23, further
comprising:
a substantially uniform diameter flow tube defining the
cross-sectional flow area within the desolvation chamber, the flow
path means, and the solvent removal means.
34. An improved method for producing particles of interest for
analysis of a sample by a detector from liquid effluent including
sample solute and solvent discharged from a liquid chromatographic
device, the method comprising;
spraying the liquid effluent into a desolvation chamber;
controllably heating the temperature of the liquid effluent in the
desolvation chamber such that substantially all solvent within the
desolvation chamber is vaporized while sample particles of interest
remain in the desolvation chamber;
inputting a selected carrier gas to the desolvation chamber;
transferring an aerosol including the carrier gas, the vaporized
solvent, and the particles of interest from the desolvation
chamber;
providing a gas diffusion membrane separating the aerosol from an
adjoining secondary flow chamber; and
diffusing solvent from the aerosol to the secondary flow chamber
for continuously removing solvent from the transferred aerosol
while outputting the carrier gas and sample particles of interest
for analysis by the detector.
35. The method as defined in claim 34, wherein the liquid effluent
is supplied to the desolvation chamber continuously while liquid
effluent including sample solute over a range of atomic mass units
is continually supplied to the interface from the liquid
chromatographic device.
36. An improved method as defined in claim 34, wherein the carrier
gas is selected as a function of the detector.
37. An improved method as defined in claim 34, wherein the carrier
gas is selected such that the detector is substantially
non-responsive to the carrier gas.
38. An improved method as defined in claim 34, further
comprising:
adding a selected solvent to the liquid effluent being sprayed into
the desolvation chamber which is more volatile than the solvent in
the liquid effluent.
39. An improved method as defined in claim 34, further
comprising:
heating the liquid effluent prior to being discharged into the
desolvation chamber; and
vaporizing a substantial portion of the solvent from the liquid
chromatographic device prior to being discharged into the
desolvation chamber.
40. An improved method as defined in claim 34, further
comprising
cooling the aerosol to condense the solvent vapor into liquid
solvent; and
removing the condensed liquid solvent while outputting the carrier
gas and the sample particles of interest to the detector.
41. An improved method as defined in claim 40, further
comprising:
providing a liquid waste drain for continuously outputting the
condensed liquid solvent; and
substantially all condensed liquid vapor flows through a portion of
a flow path to the liquid waste drain in a counterflow direction to
the flow of aerosol through the portion of the flow path.
42. An improved method as defined in claim 40, further
comprising:
cooling the aerosol at respective first and second serially spaced
locations within a condenser; and
providing a transition section between the first and second
serially spaced locations for revaporizing condensed solvent
carried on the particles of interest past the first location and
recondensing the solvent off said particles of interest at the
second location.
43. An improved method as defined in claim 34, further
comprising:
providing a substantially uniform diameter flow tube for defining
the cross-sectional flow area within the desolvation chamber.
44. An improved method as defined in claim 34, further
comprising:
regulating carrier gas flow rate into the desolvation chamber such
that the carrier gas flow rate is greater than the flow rate of
vapor discharged into the desolvation chamber.
45. An improved method as defined in claim 34, further
comprising:
positioning a discharge end of a sprayer within the desolvation
chamber; and
inputting the carrier gas within the desolvation chamber
circumferentially about the discharge end of the sprayer such that
the carrier gas within the desolvation chamber flows axially toward
the discharge end of the sprayer.
46. An improved method as defined in claim 34, further
comprising:
providing a cyrogenic trap for collecting in solid form at least
substantially all remaining solvent vapor such that substantially
only carrier gas and particles of interest are passed to the
detector.
47. An improved method as defined in claim 34, further
comprising:
the detector is a gas phase detector; and
vaporizing the particles of interest to produce vapor for analysis
by the gas phase detector.
48. An improved method as defined in claim 34, further
comprising:
inputting a selected liquid solvent to the liquid effluent
discharged into the desolvation chamber, the
selected liquid having a lower volatility than the liquid effluent
solvent to control particle size of the particles of interest
within the desolvation chamber.
49. An improved method as defined in claim 34, further
comprising:
maintaining the desolvation chamber at substantially atmospheric
pressure while the liquid effluent is sprayed into the desolvation
chamber.
50. An improved method as defined in claim 34, further
comprising:
regulating the flow of carrier gas to the desolvation chamber such
that vaporized solvent and the carrier gas flow at laminar flow
rates through a flow path prior to removal of the solvent.
51. An improved method as defined in claim 34, further
comprising:
sensing the temperature of the solvent vapor within the desolvation
chamber and generating a signal to control the heating of the
liquid effluent within the desolvation chamber to response
thereto.
52. An improved method as defined in claim 34, further
comprising:
moving a collection surface; and
depositing the particles of interest on the collection surface for
analysis by the detector.
53. An improved method as defined in claim 52, wherein:
regulating the distance between a nozzle and an axially spaced
skimmer for controllably removing carrier gas from the particles of
interest; and
the detector is an electron impact mass spectrometer.
54. An improved method as defined in claim 34, further
comprising:
adding reagent gas to the carrier gas input to the desolvation
chamber; and
the detector is a chemical ionization mass spectrometer.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to devices which interface between
liquid chromatographic units and gas phase or solid phase detectors
and, more particularly, relates to an improved interface which
utilizes controlled partial vaporization and nebulization of the
liquid effluent to transport the sample as an aerosol while
efficiently removing most of the solvent vapors.
2. Description of the Prior Art
The detection of effluent from chromatographic devices has been
applied to almost all areas of science requiring chemical analysis.
Such detectors usually involve the measurement of either (1) a bulk
property of the effluent (such as the refractive index) which is
sensitive to the presence of the sample, (2) a property of the
sample not possessed by the mobile phase (such as optical density
at a suitable wavelength), or (3) a property of the sample after
elimination of the mobile phase.
In gas chromatography (GC), the properties of the samples of
interest are often sufficiently different from suitable mobile
phases, and accordingly the second approach can generally be used
with negligible interference. The analytical power of gas
chromatography is thus widely recognized, despite the fact that
less than 20% of known organic compounds are suitable for GC
without chemical derivatization. Part of this power stems from the
wide variety of detectors which are available for routine use with
gas chromatography, such as flame ionization, photoionization, ICP,
FTIR, flame photometric, thermal conductivity, and mass
spectrometry. Certain of these detectors, e.g. flame ionization,
are almost universal, i.e. can be reliably used for analysis of a
wide range of GC samples.
In liquid chromatography (LC), the properties of the sample in the
mobile phases are often similar to those of the mobile phase
itself. An almost universal LC detector comparable to flame
ionization for GC does not currently exist. Accordingly, reliable
detection of LC samples has generally been obtained using equipment
specially designed for limited purposes. While LC is applicable to
a much broader range of samples than GC, its limited utility is
thus partially attributable to the lack of a suitable universal LC
detector.
Tremendous advances have been made during the past two decades in
LC technology, particularly with respect to high-performance liquid
chromatography (HPLC) column technology, and in the development of
improved instrumentation to monitor LC effluent to detect,
quantify, and preferably identify the eluting components. Probably
the most widely used detectors for use with HPLC are photometers,
which are based oh ultraviolet or visible light absorption
differences. While photometers have high sensitivity for many
solutes, samples must absorb in the spectral region where the
mobile phase is essentially transparent (typically 200 to 600 nm).
Those skilled in the art have long recognized that this restricted
spectral region is a serious limitation of photometric detectors,
since the strongest optical absorption bands occur for most samples
and mobile phases at shorter wavelengths.
The thermospray technique was developed primarily for coupling
liquid chromatography to a particular gas phase detector, namely
mass spectrometry. Thermospray technology provides an LC to mass
spectrometry interface which has significant advantages compared to
other coupling techniques. In thermospray technology, the LC
effluent is partially vaporized and nebulized in a heated vaporizer
probe to produce a supersonic jet of vapor containing a mist of
fine droplets or particles. As the droplets or particles travel at
a high velocity through the heated ion source, they continue to
vaporize due to rapid heat input from the surrounding hot vapor.
Thermospray thus employs controlled heating of the capillary and
the ion source to convert the LC liquid stream into gas phase ions
for introduction into the mass spectrometer. A more detailed
description of the major components and function of the thermospray
system are disclosed in U.S. Pat. No. 4,730,111.
A significant disadvantage of thermospray, as well as other direct
coupling techniques between liquid chromatographic devices and mass
spectrometers, is that ionization occurs in a bath of solvent vapor
at a relatively high source pressure (typically 1 torr or more).
This pressure effectively precludes the use of electron impact (EI)
ionization, and also limits the choice of reagents in chemical
ionization (CI). Moreover, detection utilizing thermospray
interface technology has heretofore been limited to a fairly narrow
range of chromatographic conditions, since thermospray ionization
performs best when the solvent flow rate is in excess of 1
mL/minute, and at least 20% of the mobile phase is water.
Various attempts have been made to overcome the limitations of
interfaces between liquid chromatographic units and detectors. One
commercially successful technique is similar to that described in
U.S. Pat. No. 4,055,987. This technique unfortunately involves
various moving wires and belts, and accordingly has significant
operational drawbacks which have become widely recognized by those
skilled in the art.
A second type of liquid chromatography to gas phase detector
interface is known by the acronym MAGIC, which stands for
Monodisperse Aerosol Generation Interface for Chromatography. In
this device, the LC effluent is forced under pressure through a
relatively small orifice (typically 5 to 10 microns in diameter,
such that the liquid jet breaks up into a stream of relatively
uniform droplets as a result of Rayleigh instability. A short
distance downstream, the stream of particles is intersected at
90.degree. by a high velocity gas stream (usually helium) to
disperse the particles and prevent coagulation. The dispersed
droplets proceed at a relatively high velocity through a
desolvation chamber, where vaporization occurs at atmospheric
pressure and near ambient temperature. Heating is input to the
desolvation chamber to replace the latent heat of vaporization
necessary for solvent evaporation, while not raising the aerosol
temperature above ambient. Ideally all the solvent is vaporized,
and the sample remains as a solid particle or a less volatile
liquid droplet. Further details regarding the MAGIC approach are
disclosed in an article by Willoughby and Browner published in 1984
in ANALYTICAL CHEMISTRY, Vol. 56, commencing at page 2626, and in
U.S. Pat. No. 4,629,478.
A modified version of a particle beam interface between liquid
chromatography and mass spectrometry is disclosed in a series of
recently published articles. This technique, referred to as
Thermabeam LC/MS, uses a nebulizer which may be similar to a
thermospray vaporizer. The interface includes a nebulization stage,
an expansion stage, and a momentum separation stage, each axially
connected in series. In both the MAGIC and the Thermabeam LC/MS
devices, some of the carrier gas and some of the solvent vapor is
removed in the momentum separator, but no carrier gas or solvent
vapor is removed from the desolvation chamber.
While both the second and third types of interfaces described above
apparently produce EI spectra in good agreement with library
spectra using sample injections of 100 ng or more, these spectra do
not include the low mass region where solvent interference may be
expected. Accordingly, it is difficult to determine or evaluate the
solvent removal efficiency actually achieved by these techniques.
Moreover, improved techniques are required to improve sensitivity
for gas phase detectors supplied with effluent from LC and HPLC
equipment, and to enable the detectors to be utilized over a
broader range of chromatographic conditions. Finally, an improved
interface is required which will allow LC effluent to be
transmitted for analysis to various types of gas phase detectors,
so that the flexibility and versatility of the interface is
enhanced and its costs minimized.
The disadvantages of the prior art are overcome by the present
invention, and improved methods and apparatus are hereinafter
disclosed which provide an interface for coupling liquid
chromatography to various types of gas phase detectors.
SUMMARY OF THE INVENTION
The interface of the present invention may be used with various
types of gas phase and solid phase detectors, and provides a
substantially universal solution to detection of LC effluent. The
LC solvent is vaporized and the solvent vapor is efficiently
removed, and substantially all samples (except perhaps the most
volatile) may be transferred as a particle beam and merged with a
carrier gas selected for the particular detector. Pyrolysis and
other uncontrolled chemical modifications of the sample may be
precluded during this process, and thus thermally labile and
nonvolatile components may be readily analyzed by an appropriate
detector. The techniques of the present invention are applicable to
a wide range of LC flow rates, and essentially all LC mobile phases
(even those containing nonvolatile buffers) may be used with the
interface of the present invention provided that the introduction
of the nonvolatile material can be accommodated by the particular
gas phase detector employed.
In a suitable embodiment of the present invention, the interface
includes a thermospray vaporizer in which most but not all of the
solvent is vaporized, while the remaining unvaporized material is
carried along as an aerosol in the high velocity vapor jet. The
thermospray jet is introduced into a desolvation chamber, which may
be controllably heated to further vaporize the droplets in the
aerosol. A carrier gas is added to the desolvation chamber to
maintain the desired pressure and flow rate, while the heat input
to the thermospray vaporizer and to the desolvation chamber is
adjusted so that substantially all of the solvent is vaporized
while most of the less volatile materials will be retained in the
unvaporized particles. The aerosol then passes through one or more
solvent removal chambers, where most if not substantially all of
the solvent vapor is removed, either by condensation or by allowing
it to diffuse through a membrane to a second counterflowing gas
stream. The resulting dry aerosol may then be transmitted to a
suitable detector, either directly or through a particle beam
momentum separator to increase the concentration of particles
relative to the remaining solvent vapor and carrier gas.
The flow path through the solvent removal chamber(s) preferably has
a substantially uniform cross-sectional area, such that rapid
expansion or contraction of the fluid stream is minimized, and
"dead spaces" are eliminated. A series of such chambers may be
provided, with each chamber removing a portion of the solvent
vapor. The solvent is preferably removed from the aerosol of
unvaporized sample particles and inert carrier gas in a counterflow
process, thereby enabling continuous operation of the system from
the LC to the gas phase detectors. Since the interface allows most
of the solvent to be removed while the sample is retained and
transmitted as an aerosol, several significant advantages are
obtained. When used with a particle beam momentum separator to
further reduce the pressure of vapor and carrier gas transmitted
along with the particles in the aerosol, the technique of the
present invention is particularly well suited for use with both EI
(electron impact) and CI (chemical ionization) mass spectrometry.
Limitations imposed by the transmission of large amounts of solvent
vapor in conventional approaches are obviated by the present
invention. Also, significant service problems frequently associated
with the vacuum pumps used with particle beam separators or
conventional thermospray systems are avoided, since in the present
invention the vapor load on the vacuum pumps is substantially
reduced.
It is an object of the present invention to provide an improved
interface for transmitting samples contained in an LC effluent to a
gas phase or solid phase detector.
It is a further object of the present invention to provide an
interface which provides an improved signal to noise ratio output
from the detector compared to conventional prior art techniques by
substantially reducing the amount of solvent transported to the
detector.
It is a feature of the present invention to provide an LC to gas
phase detector interface which utilizes at least one chamber for
removing solvent vapor, with the chamber having a substantial
uniform cross-sectional gas flow area.
It is another feature of the present invention that the interface
is applicable to thermospray technology, so that the controlled
partial vaporization of the gas from the thermospray capillary may
occur, with further vaporization occurring in the desolvation
chamber downstream from the capillary.
It is a further feature of the present invention that the interface
may include a plurality of solvent removal chambers connected in
series for continuously removing solvent vapor from the stream and
supplying substantially dry particles to the gas phase
detector.
It is an advantage of the interface according to the present
invention that a high degree of desired sample information relative
to background solvent information can be attained, so that little
or no loss of information occurs as a result of the solvent
interference. For example, in EI mass spectrometry, sample
molecular ions and fragments may be detected even though the masses
may coincide with major ions produced from the solvent vapor.
Another advantage of the invention is that a substantial portion of
the solvent vapor in the LC effluent is removed by the interface
prior to entering a gas phase detector, such that the service life
of pumps intended to maintain a desired system pressure level may
be substantially prolonged.
It is another advantage of the present invention that the
functional components of the interface of the present invention
need not include moving parts, so that service and reliability of
the interface is enhanced.
These and further objects, feature, and advantages of the present
invention will become apparent from the following detailed
description, wherein reference is made to the figures in the
accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram illustrating the primary components of
the liquid chromatographic device to gas phase detector interface
according to the present invention.
FIG. 2 is a simplified pictorial view of one embodiment of an
interface according to the present invention.
FIG. 3 is simplified pictural illustration of an alternative
version of a thermospray vaporizer which provides a concentric flow
of heated carrier gas.
FIG. 4 is a partial block diagram and partial pictorial view of
another embodiment of an interface according to the present
invention.
FIG. 5 is a partial block diagram and partial pictorial view of
another embodiment of an interface according to the present
invention.
FIG. 6 is a simplified pictorial illustration of a portion of an
interface according to the present invention connected to a
suitable gas phase detector.
FIG. 7 is a pictorial view of a portion of an interface according
to the present invention for depositing the sample on a solid
surface for subsequent analysis by a solid phase or gas phase
detector.
FIG. 8 illustrates a portion of an interface according to the
present invention for coupling LC to electron impact mass
spectrometry analysis.
FIG. 9 illustrates a portion of the interface according to the
present invention for coupling LC to chemical ionization mass
spectrometry analysis.
FIG. 10 is a pictorial view of a portion of an interface according
to the present invention for coupling LC to a temperature
controlled surface for laser desorption analysis.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The method and apparatus of the present invention are suitable for
coupling LC effluent to various GC detectors. In some cases, it may
be necessary to interpose means for vaporizing the sample particles
immediately prior to the detector. For many gas phase detectors, it
is not necessary to preserve the molecular integrity of the sample,
and various conventional means may be used for vaporizing the
particles even if thermal degradation of a sample occurs. Other
detectors, such as mass spectrometry and FTIR, provide information
regarding molecular weight and/or molecular structure, and
accordingly it is essential to avoid pyrolysis or other
uncontrolled chemical modification of the sample. Examples of gas
phase detectors which may be used with the interface of the present
invention are flame ionization detectors (FID), flame photometric
detectors (FPD) for specific elements (such as P and S), thermionic
ionization detectors (TID), atomic absorption (AA),
photoionization, thermal conductivity, mass spectrometry,
inductively coupled plasma detectors (ICP), and Fourier transform
infra-red (FTIR).
In order to more fully appreciate the features and advantages of
the present invention, a background discussion of vaporization and
nebulization theory in a thermospray capillary is provided
below.
Thermospray Vaporizer
When liquid is forced at high velocity through an unheated
capillary tube, a solid jet issures from the tube, and breaks up
into regular droplets according to Rayleigh's theory of liquid jet
stabilty. Break up leads to droplets with uniform diameters
approximately 2 times the diameter of the nozzle, and a train of
droplets of a uniform size and velocity are thus produced. If the
tube is heated gently, the properties of the jet are modified
slightly by the drop in surface tension accompanying the increase
in temperature, although little change is visually observed. When
enough heat is applied to produce significant vaporization inside
the capillary, the appearance of the jet changes drastically as it
is partially vaporized and nebulized into a very large number of
small droplets. A further increase in the applied heat reduces the
visibility of the jet since the size of the droplets decreases due
to further vaporization at high enough heat, and the only visual
evidence of the jet is downstream condensation which occurs due to
cooling.
A detailed analysis of the process occurring when liquid is
vaporized as it is forced through a heated capillary tube is set
forth in U.S. Pat. No. 4,730,111 and pending U.S. Application
Serial No. 202,093 filed June 3, 1988, each hereby incorporated
herein by reference. For purposes of the present discussion, it
should be understood that the rate of vaporization, Z, of a liquid
at temperature, T, is given by an equation
where Pv(T) is the equilibrium vapor pressure at temperature T, Pa
is the ambient pressure of the vapor, m is the molecular mass, and
k is Boltzmann's constant. The effective vaporization velocity,
V.sub.v, may be obtained by multiplying the molecular mass and
dividing by the density, .rho..sub.L, of the liquid, such that
The thermospray vaporizer shares many of the properties of a
concentric pneumatic nebulizer used in atomic spectroscopy, in that
a high velocity gas is used to shatter a liquid stream into a fine
jet of droplets swept along in a gaseous stream. A significant
feature of thermospray is that the nebulizing gas is generated in
situ by partial vaporization of the liquid. Various attempts have
been made to directly measure the droplet size distribution
produced by thermospray, but these efforts have met with limited
success primarily because a very large number of small, high
velocity droplets are produced.
The total number of droplets produced per second N.sub.d may be
determined by the volume of the unvaporized liquid divided by the
average volume of the droplets at the instant of nebulization from
the bulk liquid. This relationship may be expressed as
where F is the liquid flow rate expressed in mL/min., f is the
fraction vaporized, and d is the droplet diameter in microns.
The rate of vaporization of a spherical liquid droplet, in turn,
can be expressed by the equation
where r is the radius of the droplet, and V.sub.v is the net
vaporization velocity calculated according to Equation 2. Since
this rate is independent of r, the isothermal lifetime of a droplet
can be expressed as a function of vaporization velocity. For water
particles at 200.degree. C. in the presence of water vapor at one
atmosphere, the net velocity of vaporization is about 100 cm/sec.
The isothermal lifetime of water droplets under these conditions is
about 1 microsecond per micron radius. At 100.degree. C., water
droplets and its vapor at one atmosphere are in equilibrium, and
the net rate of vaporization is zero. The very strong dependence of
vaporization rates on temperature thus implies that the thermal
environment of the droplet particles must be properly controlled
for efficient vaporization and ion production.
It should be noted that the above analysis contains several
unstated approximations and assumptions, which are probably not
strictly valid. For example, it is assumed throughout that a single
temperature characterizes the walls of the vaporizer, the vapor,
and the liquid at any point along the vaporizer. Since heat is
conducted from the walls of the vaporizer through the vapor to the
liquid droplets, it is apparent that significant temperature
differences must be involved.
If the initial droplet diameter and its thermal history were
precisely known, then the droplet vaporization lifetime could be
accurately calculated. In the absence of such detailed information,
the parameters can be adjusted emperically to achieve complete
vaporization of the solvent in the droplets at the exit from the
desolvation chamber of the interface. The parameters which affect
the droplet lifetime within the interface of the invention are
accordingly the thermospray vaporization parameters, namely the
temperature of the jetstream from the vaporizer, the diameter of
the droplets, and the temperature and pressure of the carrier gas
added to the desolvation chamber, which then determines the heat
transfer to the droplets. If the sample is expected to contain
components only slightly less volatile than the solvent, it may be
necessary to carefully adjust thermospray conditions for the
interface to achieve satisfactory transmission of volatile sample
components while simultaneously efficiently removing the
solvent.
LC to Detector Interfaces
Referring now to the drawings, FIG. 1 illustrates a block diagram
of an interface according to the present invention. Effluent from a
liquid chromatography (LC) unit 10 is directly coupled to a
thermospray vaporizer 12, in which a controlled percentage of the
solvent is vaporized while the remaining unvaporized solvent and
sample particles are carried along as an aerosol in a high velocity
vapor jet. The thermospray operation is carefully regulated by
controller 14, which is described in detail in U.S. Pat. No.
4,730,111. The jet from the thermospray vaporizer 12 is introduced
into a desolvation chamber 16, which may be heated sufficiently to
further the vaporization process. Additional compressed and
preferably inert gas, e.g. dry air, helium, or argon, is added from
source 18 to the chamber 16 in sufficient quantity to maintain the
desired pressure and flow rate. The flow rate of carrier gas may be
carefully regulated by valve 19, as described below. The
temperature of the desolvation chamber is closely regulated by
temperature controller 20, so that all or essentially all of the
solvent is vaporized within the chamber 16. The thermospray
technique of the present invention allows very precise control of
vaporization, so that the solvent can be vaporized while all or
substantially all of the less volatile particles of interest will
be retained. An aerosol consisting of vaporized sample particles,
solvent vapor, and inert carrier gas will exit the desolvation
chamber 16 and pass through one or more solvent removal chambers
22, where most of the solvent vapor is removed and discharged to
liquid waste container 24. The resulting dry aerosol (unvaporized
sample particles and inert carrier gas) is then transmitted to the
gas phase detector 28, either directly or through one or more
particle beam separators. The gas phase detector may be responsive
to the sample particles of interest or to vapor from the sample
particles of interest. In the latter case, a vaporizer 27 is
provided between the condensers and the detector to achieve
varporization of the particles of interest.
In one embodiment of the invention, the temperature of the
desolvation chamber 16 is closely controlled by controller 20,
while the temperature of the solvent removal chamber(s) 22 is
controlled by temperature controller 26 so that solvent is removed
by condensation, and the dry aerosol continues to the selected
detector. The solvent vapor is thus carefully condensed by
regulating controller 26 and the condensed solvent passed to waste
container 24 while the less volatile materials continue on
unaffected by the condensation process.
When thermospray is used to partially vaporize and nebulize the LC
effluent, the desolvation 16 need not be controlled by a separate
temperature controller 20, since the temperature of the spray in
desolvation chamber 16 is sufficiently controlled by the vaporizer
itself. For operation in this mode, it is preferable to operate the
thermospray vaporizer close to, but below, the point of complete
vaporization so that the vapor droplets exiting the vaporizer have
sufficient heat content to provide the heat necessary to complete
the vaporization during the expansion of the jet. Nevertheless, a
separately heated desolvation chamber regulated by a controller 20
provides a convenient technique for completing the vaporization
process started by the thermospray, and this temperature controlled
desolvation chamber will often be required when using other types
of nebulizers.
Referring now to FIG. 2, an embodiment of the interface is depicted
in which the desolvation chamber employs a refrigerated condensor
to remove the solvent vapor. In FIG. 2, the discharge end 30 of a
thermospray vaporizer (which is fully described in U.S. Pat. No.
4,730,111) is installed in the desolvation chamber 34, such that a
gas-tight connection is made between the vaporizer and the
desolvation chamber. Controlled partial vaporization of solvent
being discharged from end 30 is obtained by heater block 29 about
the discharge end. The desolvation chamber 34 as shown in FIG. 2 is
structurally a part of the solvent removal chamber, which in the
depicted embodiment is a condenser, although it should be
understood that a structurally separate desolvation chamber and
condenser may be provided. The temperature within the chamber 34 is
maintained by a sleeve-like heat block 36 in thermal contact with
tube 40 to obtain the desired vaporization of the solvent in the LC
effluent. A thermocouple 37 may thus be responsive to the
temperature within chamber 34, to the temperature of the tube 40 in
the heated zone of the desolvation chamber (as shown in FIG. 2), or
to the temperature of the block 36. The output from thermocouple 37
is thus input to temperature controller 20, which regulates the
heating of 36 to obtain the desired vaporization. The zone of the
interface heated by block 36 should be sufficiently long to allow
the particles to approch their thermal equilibrium with the vapor
phase. The minimum temperature for complete vaporization of the
solvent is then the temperature at which the vapor pressure of the
solvent is just greater than the partial pressure of the completely
vaporized solvent at the particular flow rate of the liquid
employed. Ideally, effluent from the desolvation chamber 34
consists of nearly dry particles of unvaporized sample, solvent
vapor at a partial pressure somewhat less than one half of the
total pressure, and carrier gas.
An appropriate carrier gas is introduced into the desolvation
chamber 34 through port 38, and preferably flows in the annulus
between the chamber interior sidewalls 35 and the vaporizer probe
30 to entrain the droplets produced in the thermospray jet. At the
discharge end of the thermospray probe 30, the carrier gas is thus
moving axially with and surrounds the thermospray jet. In general,
the flow rate of the carrier gas should be at least equal to the
vapor flow produced by the complete vaporization of the liquid
input to the vaporizer. If the LC sample contains volatile
components, however, it may be desirable to use a higher gas flow
rate so that the liquid can be vaporized at a lower
temperature.
Instead of a standard thermospray vaporizer as described above, a
modified thermospray vaporizer 128 such as that depicted in FIG. 3
may be employed. In this configuration, the liquid from the
chromatograph is carried through an inner capillary tube 130 which
may be conveniently made from fused silica or from stainless steel
hypodermic needle tubing. An outer tube 132 of stainless steel is
heated directly by passing a current through it, and the heat input
is controlled as described in detail in U.S. Pat. No. 4,730,111.
The carrier gas is transmitted through the annular space 134
between the inner and outer tube. With this device, both the LC
effluent and the carrier gas are heated and the high velocity of
heated carrier gas discharged surrounding the thermospray jet 136
assists in dispersing and vaporizing the droplets in the jet.
Although flow velocities through the interface are not critical,
carrier gas flow must be sufficiently high to effectively transport
the aerosol while causing minimal turbulence. A tube 40 with a
circular interior cross-section of a diameter approximating one
centimeter is satisfactory for flow rates obtained with LC liquid
inputs up to at least 2 mL/minute. A uniform cross-section of the
flow path throughout the desolvation chamber and condensers is
preferred, and sudden changes in the cross-section which would
result in rapid expansion or contraction of the flow rate should be
avoided. Although the aerosol may be passed through an arcuate
path, as shown in FIG. 2, sharp bends in the flow path should be
avoided so that particles do not impact the interior sidewalls of
the tube 40 and accordingly may pass to the selected detector.
Under preferred flow conditions, essentially laminar flow is
maintained in tube 40, and the aerosol is carried by the higher
velocity carrier gas through the center of the tube, thereby
allowing the particles to be transported along comparatively long
distances with negligible losses. In view of the large mass of
these particles relative to that of the carrier gas and solvent gas
molecules, diffusion of the aerosol particles to the walls is
small, while diffusion of solvent molecules in the carrier gas is
relatively rapid.
As effluent passes through tube 40 from the heated zone of the
desolvation chamber to the cooler zone of the condenser, it becomes
supersaturated and begins to condense on the walls of the tube 40.
Condensation of vapor on the sample particles will be minimal since
the sample particles near the center of the tube 40 will normally
be somewhat warmer than the vapor in contact with the cooler walls,
and since the total surface area of the particles will normally be
considerably smaller than the surface area of the cool tube. The
temperature of the sleeve-like cooling jacket 42 in thermal contact
with the tube 40 may be adjusted so that the inner wall temperature
is only slightly above the freezing point of the condensed liquid.
A thermocouple 43 is provided for sensing and transmitting to
controller 26 a signal indicative of the inner wall temperature in
the condenser, and controller 26 regulates jacket 42 in response
thereto.
The tube 40 is thus provided with a transition region or section 41
between the heated zone of the desolvation chamber and the cooled
zone of the condenser. The transition region 41 is arranged, as
shown in FIG. 2, so that the liquid condensate 44 preferably flows
under the affects of gravity to the drain 46 in the transition
region 41 of tube 40, where the condensate is pumped away to waste.
A small positive displacement pump 48, such as a peristaltic tubing
pump, may be used to pump away the condensate without allowing a
significant amount of gas or vapor to escape from the interface.
The drain may be equipped with a conventional check valve 50 to
prevent backflow of liquid in the event that the interior pressure
of the interface should drop below the outside pressure.
Assuming a sufficient length of cool zone is provided in the
condenser, the vapor exiting the condenser approaches equilibrium
with the liquid at the temperature of the condenser. A condenser
employing a straight tube approximately 30 centimeters in length
has been found to be satisfactory for LC liquid input flow rates up
to 0.5 Ml/minute. The length of the flow path from the desolvation
chamber to the condensers should be at least 30 times, and
preferably at least 50 times, the diameter or width of the flow
path. For applications at higher liquid flow rates, the total
length of the cool zone should be increased in proportion to the
maximum liquid flow anticipated. The condenser can be configured to
cool the tube 40 arranged in a helical form, thereby effectively
increasing the cooled length of the tube 40 without increasing the
size of the condenser. A helical pattern for the tube 40 would also
introduce some angular momentum into the flow, which can increase
the effective diffusion coefficient and correspondingly increase
the efficiency of the condenser.
A relatively simple interface as depicted in FIG. 2 may provide
efficient solvent removal for some LC to gas phase detector
applications. For example, if the detector is an electron impact
mass spectrometer equipped with a two-stage particle beam separator
which further reduces solvent vapor transmission, the combination
of the interface and the particular detector may result in
efficient solvent removal efficiency while transmitting more than
one half of the sample particles. The embodiment shown in FIG. 2
may thus result in good detector sensitivity for many samples, even
though there is still significant contribution to the low mass
portion of the mass spectrum by ionization of solvent vapor. With
the condenser as depicted in FIG. 2 cooled to 0.degree. C., more
than 99% of the water can be condensed and removed, while more than
90% of typical organic solvents, such as methanol or acetonitrile,
may be removed. The condensor of the present invention is able to
remove substantially all, and preferably at least 90% of the
solvent in the LC effluent which is discharged into the desolvation
chamber. Solvent removal efficiency of more than 95% can be
obtained by programming the temperature of the condenser according
to the composition of the LC mobile phase. The temperature of the
condenser should, however, not be less than the freezing point of
the liquid mixture input, or solid waste build up in the condenser
may clog the interface. Since it is often desirable to detect
samples separated by liquid chromatography at concentrations at the
part per billion level or even lower, a further reduction in
solvent concentration beyond that obtainable with the interface as
shown in FIG. 2 may be required for many applications.
FIG. 4 depicts a system which will enable a further reduction in
solvent vapor concentration compared to the interface as shown in
FIG. 2. The interface as shown in FIG. 4 includes a first stage
condenser 52, which may be structurally and functionally identical
to that depicted in FIG. 2. A second stage condenser 54 is added in
series to first stage condenser 52, with the second stage unit 54
being structurally similar to that shown in FIG. 2, but with no
additional carrier gas or thermospray jet provided, and thus no
heated zone or block 36. Accordingly, the second stage condenser 46
comprises a U-tube in series with the U-tube of the first stage
condenser, a second stage drain, and a second stage cooled zone or
jacket 42 downstream from the drain. An cyrogenic trap 56 as shown
in FIG. 4 is then added in series after the second stage condenser
54, with its effluent passing to a suitable gas phase detector,
such as an EI mass spectrometer 58.
For the interface depicted in FIG. 4, the first stage condenser 52
is preferably operated at a temperature just above the freezing
point of the input solvent composition, while the second stage
condenser 54 is preferably operated at a temperature just above the
freezing point of the remaining solvent vapor composition
transmitted by the first condenser, so that the second stage
condenses without freezing the maximum amount of solvent vapor.
Between the first and second condenser stages, the vapor and
aerosol pass through a section of tube 0 maintained at ambient
temperature. This allows any solvent which may have condensed on
the particles in the first stage condensers 54 to be revaporized,
and subsequently condensed off the particles in the second stage
condenser 56 with most of the remaining vapor. If the second stage
condenser is operated at approximately -40.degree. C., then more
than 99% of organic solvents will be removed by the first and
second stage condensers, along with all or almost all of the water.
If a further reduction of solvent vapor concentration is required,
the effluent from the second stage condenser 54 may be transported
through tube 60 which is positioned within a sealed housing 62
immersed in a suitable coolant, such as a liquid nitrogen. The
housing 62 may thus contain a liquid nitrogen inlet 61 and an
outlet 63 which maintain the tube 60 at a sufficiently low
temperature to effectively remove most of the remaining solvent
vapor. This cyrogenic trap 56 thus will cause almost all of the
remaining solvent to be trapped in solid form on the inner surface
of the tube. Unlike the first and second stage condensers in which
the condensate is continuously withdrawn in liquid form, cyrogenic
trap 56 cannot be operated continuously. However, since only a
small amount of condensable material is transmitted to the trap 56
from the second stage condenser 54, it can be operated for extended
period (more than 8 hours) until sufficient solid buildup on the
inside of tube 60 has occurred to require its removal. Removal of
the buildup may be accomplished by closing the valve 68 connecting
the output of the trap 68 to the detector, and removing the
nitrogen coolant. By allowing the trap to warm to room temperature
and then opening the drain valve 64, the accumulated condensate
will be blow out past check valve 66 to waste.
The performance of the interface according to the present invention
depends to some extent on the size of the particles produced.
Smaller particles are easily accelerated in the spray nozzle, and
are also more easily deflected by flowing gas streams downstream of
a nozzle. On the other hand, larger particles are more difficult to
accelerate and require higher carrier gas velocities to maintain
them as an aerosol, but once accelerated are not easily deflected
from the particle beam. In the absence of nonvolatile material
other than the sample of interest in the liquid stream, the final
diameter of the dry particle will depend on the sample
concentration in the unvaporized liquid. This feature may have the
undesirable effect that the sample transfer efficiency may depend
on the final particle size and hence the concentration of the
sample in the unvaporized liquid, so that there is non-linearity in
the detector response, particularly at low sample concentrations.
This undesirable effect may be avoided by adding to the mobile
phase a low concentration of a material, e.g., urea, having lower
volatility than the solvent, so that its concentration rather than
that of the sample determines the final particle size. If this
added material is selected so that the detector does not respond
significantly due to its presence, then the desired linear detector
response to samples of interest can be achieved, and high detector
sensitivity maintained. Also, the selected material may be chosen
to enhance gas phase detection of selected types of compounds,
while surpressing detection of compounds of little or no
interest.
An alternative method for accomplishing solvent vapor removal is
depicted in FIG. 5. In this embodiment, the refrigerated condensors
are replaced by a gas diffusion cell 140. A "wet aerosol" mixture
142 consisting of carrier gas, solvent vapor, and sample particles
from the desolvation chamber 16 enters the diffusion cell 140, and
a "dry aerosol" mixture 144 consisting substantially of carrier gas
and sample particles of interest passes to the detector 146. The
sample particles passing through the diffusion cell are separated
from a supplemental carrier gas flow by a diffusion membrane 146.
Gas, preferably chemically identical to the carrier gas introduced
to the desolvation chamber, is input from container 148 into the
diffusion cell housing 150, and flows in the annulus 152 between
the housing 150 and membrane 146 in a counterflow direction to the
flow of particles through the diffusion cell. In this device, the
flow rate of the counterflowing supplemental gas must be
significantly greater than the flow rate of the wet aerosol
mixture, and is preferably two or more times greater, so that at
each point along the membrane 146 the concentration of solvent
vapor in the counterflow gas is significantly lower than that in
the wet aerosol. The flow rate of supplemental carrier gas 154 may
be closely controlled by valve 156. The properties of the membrane
146 are not critical, and a variety of filter media have been used
successfully. The membrane should be sufficiently permeable that
the carrier gas and vapor can diffuse freely across it, yet be a
sufficient barrier to flow that any net flow of gas through the
membrane is relatively small, and so that no particles of interest
pass therethrough. A membrane formed from a fibrous porous form of
PTFE has been found to be satisfactory, and such a suitable
material is commercially available under the tradename "ZITEX."
The above approach has the advantage over the refrigerated
condensors since no expensive mechanical components, such as
refrigerators and pumps, are required, but has a minor disadvantage
in that a higher total flow of carrier gas is required. The
effective area of the diffusion cell, i.e., the area of membrane
146 separating the particles in the primary flow from the
supplemental carrier gas 154, may be easily controlled to remove
the desired amount of solvent vapor. Also, the gas diffusion cell
140 may be used in series with the refrigerated condensors. For
example, the diffusion cell 140 may replace the cryogenic trap
discussed previously and shown in FIG. 4, so that a combination of
first and second stage refrigerated condensors 52 and 54 followed
by a diffusion cell 140 provides the desired solvent removal.
Once the sample has reached the specific detector desired, it may
be treated as required by the properties of the particular
detection device employed in order to attain maximum detection
efficiency for the sample. With gas phase detectors such as PID or
FID, the sample particles can be extensively heated in the gas
stream and caused to impact on a heated surface, since pyrolysis is
not detrimental and only a portion of sample need be converted to
gas so that it may be detected. In other cases, additional
conventional elements may be required to complete the coupling
between the interface and the paticular detector. Those skilled in
the art should thus appreciate that the interface of the present
invention can be combined with almost any of the wide range of gas
phase and solid phase detectors, so that an essentially "universal"
detector between liquid chromatography and gas phase detectors is
obtained.
Detector Applications
The interface of the present invention may be effectively used for
coupling LC effluent to a wide variety of detectors. Referring now
to FIG. 6, a portion of an interface 70 is shown which, in
accordance with the foregoing description, converts aerosol samples
72 less volatile than the LC solvent into a particle beam 73 which
is efficiently transmitted to a gas phase detector 28. Solvent
vapor is efficiently removed and replaced with a carrier gas at
essentionally atmospheric pressure, the added gas being suitable as
a carrier gas for use with the particular selected detector.
According to one embodiment, the aerosol from one or more
condensers 22 may be directly input at atmospheric pressure through
flow tube 74 to a selected gas phase detector 28, which is vented
to atmosphere.
For other gas phase detectors, it may be necessary to reduce the
flow rate to the detector and provide a heating means to vaporize
the particles to provide a sample vapor which can be detected. FIG.
6 illustrates a flow tube 74 from one or a series of condensers 22,
wherein the aerosol flow (rate of from 0.5 to 2.0 L/minute) is
substantially restricted at nozzle 75, which discharges a particle
beam through momentum separator 76 and into tube 80. Gas or vapor
may thus be vented from separator 76 through vent line 78, so that
the beam 73 in tube 80 is at substantially atmospheric pressure.
The flow rate in the tube 80 may be restricted, for example, by
entrance skimmer 81, so that the detector 28 may be vented to
atmosphere at 84, with vent 84 discharging a small fraction, e.g.
from 10 to 100 mL/min., of the flow rate from the condensers 22.
The tube 80 depicted in FIG. 6 is shown with a sleeve-like heating
unit 82 in thermal contact with tube 80 to vaporize the sample
particles passing through the tube 80, and thus transmit a sample
vapor to the detector 28. For still other gas phase detectors, it
may be possible to accomplish vaporization of the sample particles
directly as the sample is ionized and detected, e.g. in a
flame.
FIG. 7 depicts a portion of a thermospray interface according to
the present invention coupled to a detector 28 which is responsive
to sample deposited on a solid surface. Accordingly, the flow tube
74 from the condensers is restricted by nozzle 75 to discharge a
particle beam 73 which impinges a moving or movable surface 86,
such as a ribbon, plate, or drum. The sample separated by liquid
chromatography are thus deposited at different locations on the
moving surface 86, and can subsequently be analyzed or detected by
an appropriate surface sensitive technique, such as diffuse
reflectance FTIR, secondary ion mass spectrometry (SIMS) or Cf-252
plasma desorption mass spectrometry. In each of these cases, a
solid may be added in solution to the mobile phase upstream of the
vaporizer, which can then serve as a solid carrier to enhance the
transmission of samples of low concentration to the detector 28,
and also enhance detection of the samples of interest. For example,
potassium chloride could be added to provide a transparent matrix
for FTIR detection. Alternatively, organic solids such as
nitrocellulose or tartaric acid, may be added upstream of the
vaporizor to enhance the performance of a mass spectrometry
detector.
FIG. 8 illustrates a thermospray interface according to the present
invention used to couple liquid chromatography to electron impact
mass spectrometry. Since EI mass spectrometry requires a relatively
good vacuum in the ion source and mass analyzer, additional pumping
capability is provided to reduce the pressure of the carrier gas
before it reaches the ion source, while simultaneously efficiently
transmitting the particle beam. As illustrated in FIG. 8, tandem
momentum separators are employed, and the selected carrier gas is
preferably a low molecular weight inert gas, such as helium. The
discharge from flow tube 74 passes through a first momentum
separator 88, which is evacuated to a pressure of a few torr by a
suitable mechanical vacuum pump 96 with the capacity of
approximately 4 liters per second. The particle beam continues to
pass through tube 92, with the flow rate further reduced by skimmer
81 as previously described, and is discharged into a second
momentum separator 94 evacuated to a pressure of about 0.001 torr
or less by a diffusion pump 96 with a capacity of about 400 liters
per second. By properly choosing the nozzle and skimmer orifices,
and by regulating the distance between the nozzle 75 and the
skimmer 81 in either or both of the first and second momentum
separators 88 and 94, the remaining particle beam may be
effectively transmitted to the EI ion source 98 and the mass
spectrometer 100, while most of the carrier gas is pumped away by
90 and 96. A small fraction of the carrier gas may, of course,
reach the ion source 98, but a low mass and small ionization
cross-section carrier gas (e.g. helium) in small concentration will
not seriously degrade the performance of the EI mass spectrometer,
e.g. when its pressure is less than about 0.0001 torr. As shown in
FIG. 8, the EI ion source 98 and mass analyzer 100 may be
conveniently housed within chamber 102, in which vacuum is
effectively controlled to the extent desired for EI mass
spectrometry by pump 104.
FIG. 9 depicts a thermospray interface for coupling liquid
chromatography to chemical ionization mass spectrometry. This
technique is similar to that employed for EI mass spectrometry, but
only a single momentum separator is required, since the CI ion
source 106 operates at a much higher pressure of, for example, 1
torr. The aerosol thus passes through a single momentum separator
88 as shown in FIG. 8, with the particle beam 73 continuing through
tube 92A similar to that shown in FIG. 8. In this case, however,
the particle beam is directly input to CI ion source 106, and the
ions passed through baffles 108 and analyzed by mass analyzer 100A.
The CI ion source 106 and analyzer 100A are appropriately housed in
chamber 102A, with the necessary vacuum for CI mass spectrometry
regulated by pump 104A. In this case, a desired chemical ionization
reagent gas may be introduced with the carrier gas to the
interface, or helium can be used as the carrier gas and the reagent
introduced directly into the ion source 106 at a very low flow
rate.
FIG. 9 depicts a thermospray interface for transmitting a sample
particle beam to a surface in an evacuated detection instrument.
The detector in the particular configuration depicted is for laser
desorption mass spectrometry, although secondary ion mass
spectrometry, matrix isolation FTIR, or other detector requiring a
high vacuum may be used. For FTIR, argon may be used as the carrier
gas so that a small fraction of the transmitted gas impacts a
cyrogenically cooled surface upon which both the sample and the gas
are condensed and subsequently analyzed. The impacted surface may
be either heated or cooled, and the sample contained in the
particle beam 73 may be collected on the surface and simultaneously
vaporized, or ionized by either focused laser radiation or by
impact from high energy ions or neutrals. Alternatively, the
samples may be vaporized by heating the surface, either directly or
by irradiation from a laser or ion beam, and the samples then
vaporized and ionized by electronic impact using auxillary electron
beam techniques. FIG. 10 thus depicts a flow tube 92B similar to
that previously described for receiving aerosol passed through a
single momentum separator 88, and transmitting the particle beam 73
to a second momentum separator 94A with its vacuum maintained by
vacuum pump 96A. The particle beam continues on to impact
temperature controlled surface 118, where the sample is vaporized
and ionized by laser beam 120 input to chamber 114 through port
122. The sample ions 126 pass through baffles 124, and thence to
mass analyzer 100C. Appropriate vacuum for the analysis is
maintained by pump 116.
It should be understood that various nebulizers may be used for
discharging an LC effluent spray into a desolvation chamber
according to the present invention, although thermospray techniques
which include the controlled partial vaporization of the effluent
prior to discharge are preferred. Also, if a nebulizer technique
other than thermospray is used, it would be preferred to heat the
LC effluent prior to spraying into the desolvation chamber, so that
complete vaporization of the solvent in the desolvation chamber can
reliably occur at reasonable LC flow rates without significant
vaporization of the sample particles of interest. The techniques of
the present invention are applicable, however, to various
nebulizers for discharging LC effluent into the desolvation
chamber, such as variations of the MAGIC or thermabeam concepts
discussed earlier.
It should also be understood that a particular solvent may be
selected for carrying the samples of interest (solute) through the
chromatographic device which will be dependent upon the selected
chromatographic unit and the samples to be separated by the
process. Preferably, there is a significant disparity between the
volatility of the solvent and the volatility of the samples of
interest, such that complete vaporization of the solvent occurs
within the interface of the present invention without there being a
significant vaporization of the samples of interest.
It should be understood that various types of gas phase and solid
phase detectors may be used with the substantially universal
interface of the present invention for coupling LC effluent to a
desired detector. Although some modifications of the equipment
downstream from the desolvation chamber and condensers may be
beneficial or necessary, the same basic interface may be used with
various gas phase detectors, thereby enhancing versatility of the
interface and reducing manufacturing costs.
The foregoing disclosure and description of the invention is
illustrative and explanatory thereof, and various changes in the
size, shape and materials as well as in the details of the
illustrated construction may be made within the scope of the
appended claims without departing from the spirit of the
invention.
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